Representative examples of applications research based on Free-Electron Lasers are reviewed. Research highlights include: observation of absolute negative conductance in semiconductor superlattices using a terahertz Free-Electron Laser at the University of California, Santa Barbara; infrared photon echos as a technique in nonlinear spectroscopy to investigate vibrational dynamics in liquids and glasses using an infrared Free-Electron Laser at Stanford University; attributing the 20.1 μm stellar spectral feature to titanium carbide clusters using an infrared Free-Electron Laser in The Netherlands; human laser neurosurgery and ophthalmic laser surgery using an infrared Free-Electron Laser at Vanderbilt University; imaging of nanoscale island dynamics during thin film growth using the ultraviolet Free-Electron Laser at Duke University; and nuclear resonant fluorescence measurements for parity assignments in 138Ba using the high intensity gamma ray source at Duke University.